Globally, the number of diabetic patients continuously increases. Various complications caused by chronic hyperglycemia due to diabetes threaten QOL and life of the patients, which has become a serious problem.
The so-called three major diabetic complications: diabetic nephropathy, diabetic retinopathy and diabetic neuropathy are developed due to organ damage caused by microangiopathy, which is a pathological change occurring in thin blood vessels, mainly capillaries. These complications can be prevented to a certain extent by appropriately controlling blood glucose with dietary therapy, drug therapy or the like. However, when the complications become serious, there is no fundamental therapy.
It is known that mesenchymal stem cells (hereinafter, also referred to as “MSCs”) are cells capable of differentiating into not only mesenchymal cells but also diverse cells beyond the germ layer and have an ability of controlling the tissue development, repair and reproduction.
Since the isolation and cultivation of mesenchymal stem cells are easy and mesenchymal stem cells have a vigous proliferation potential, it is possible to ensure the number of transplantable cells in a short period. In addition, mesenchymal stem cells can be transplanted autologously with no immunological rejection, which causes few ethical problems. Furthermore, allogenic transplantation of mesenchymal stem cells without pretreatment is realistic because of their low immunogenicity. Accordingly, the therapeutic applications of mesenchymal stem cells as a material for ideal cell transplant therapy for diverse diseases are proceeding.
For example, the therapeutic effects of mesenchymal stem cells have been confirmed in diabetes and its complications described above (Non Patent Literatures 1 and 2) as well as diseases such as brain and cardiovascular disease (Patent Literature 1), autoimmune disease (Non Patent Literature 3), experimental autoimmune encephalomyelitis model of multiple sclerosis (Non Patent Literature 4), and inflammatory disease (refer to Non Patent Literature 5 on pulmonary fibrosis model, refer to Non Patent Literature 6 on inflammatory bowel disease).
When used for disease therapy, it is necessary to prepare mesenchymal stem cells with a certain level of quality rapidly and in a large amount. In order to allow the mesenchymal stem cells obtained from donors to proliferate in vitro, growth promoting substances, cell culture substrates and the like are variously examined. For example, Patent Literature 2 discloses that an umbilical cord extract can be used as a serum alternative on cultivation of stem cells in a serum free medium. Concerning the quality of cells, for example, Patent Literature 3 discloses a cell growth medium for suppressing senescence of mesenchymal stem cells during subculturing.
However, the umbilical cord extract disclosed in Patent Literature 2 is simply the serum alternative. The medium in Patent Literature 3 intends to maintain the quality or suppress the degree of deterioration of mesenchymal stem cells during in vitro proliferation, and does not improve or modify the quality of mesenchymal stem cells that are not appropriate for therapy, i.e. low quality mesenchymal stem cells.